The resident epithelial cells are sentinels of host defense between the organ and all external threats. Epithelial cells such as keratinocytes are known to participate actively in the immunomodulation responses through their ability to produce biologically active molecules. The regulation of IL-18 in epithelial cells is thus to significant biologic relevance to host defense. The understanding of mechanisms underlying the regulation of IL-18 may result in development of therapeutic strategies for the pathophysiology of dysregulated expression of this cytokine in the epidermal tissue. The underlying rationale of research that is proposed in this application is designed to provide us with the necessary biologic materials to formally investigate the regulatory mechanisms of IL-18 expression. Based on our observations of IL-18 expression in HK vs HCEC, we therefore hypothesize that the expression of human IL-18 in epithelial tissue is likely to be a highly regulated event that is cell type- and stimulus-dependent.